Gene Influences Tamoxifen Response

The effectiveness of tamoxifen in preventing breast cancer is lower among women who carry a gene variant linked with poor tamoxifen metabolism. These results were presented at the 2007 San Antonio Breast Cancer Symposium (SABCS).

Pharmacogenomics refers to the study of inherited variations in genes that influence an individual’s response to drugs. The goal of pharmacogenomics is more individualized cancer treatment. If doctors are able to predict in advance how an individual patient will respond to a particular drug, ineffective or harmful treatments can be avoided.

For example, researchers have found that response to tamoxifen is influenced in part by a gene known as CYP2D6 that controls tamoxifen metabolism (the processing of tamoxifen by the body). A majority of people have two functional versions of this gene and are able to effectively process tamoxifen. Some people, however, have versions of the gene that appear to reduce tamoxifen effectiveness. Testing patients for these gene variants could allow patients with the variants to choose other approaches to treatment.

Women who were classified as poor metabolizers of tamoxifen on the basis of their CYP2D6 genotype were more likely to develop breast cancer than other women.

This study provides additional evidence that CYP2D6 genotyping plays an important role in predicting tamoxifen response.

In another study presented at SABCS, researchers evaluated how CYP2D6 genotype influenced tamoxifen adherence.[2] Women who effectively metabolize tamoxifen may be more likely to experience not only the benefits of tamoxifen therapy, but also the side effects (such as hot flashes). This could lead to higher rates of tamoxifen discontinuation among effective metabolizers.

The study involved 297 women with breast cancer, 28 of whom stopped taking tamoxifen during the first year of treatment as a result of side effects. Women who effectively metabolized tamoxifen were more likely to stop taking tamoxifen than women who were poor metabolizers.

This study suggests that the patients who are most likely to benefit from tamoxifen are also the ones who are most likely to stop taking tamoxifen due to side effects. Identifying these patients in advance, and taking steps to manage tamoxifen side effects, may improve tamoxifen adherence and effectiveness.